The effect of liquid crystalline structure on chlorhexidine diacetate release

The aim of this study was to examine different liquid crystalline preparations containing chlorhexidine diacetate and to find connection between their structure and the kinetic of drug release. Nonionic surfactant, Synperonic A7 (PEG(7)-C(13-15)) was selected for the preparation of the examined liquid crystalline systems. Mixtures of different ratios of Synperonic A7 and water were produced. By increasing the water content of the systems, lamellar and hexagonal liquid crystal structures were observed. For the analysis of the prepared liquid crystalline systems polarising microscopy, rheology study, differential scanning calorimetry and dynamic swelling tests were carried out. The chlorhexidine diacetate release was examined by Franz-type vertical diffusion cell apparatus. The chlorhexidine diacetate release from hexagonal liquid crystalline preparations was characterised by zero-order release kinetics, while the drug release from lamellar liquid crystalline systems was described by anomalous (non-Fickian) transport. The results indicate that the drug release kinetic is strongly dependent on the liquid crystalline structure.     

透明质酸家族成员抗肿瘤治疗的研究进展

透明质酸(HA)是一种存在于细胞周基质和细胞外基质的非硫酸化糖胺聚糖,在肿瘤的发展和转移中起着重要作用。HA家族成员(透明质酸合成酶、透明质酸受体、透明质酸酶)已被证实能促进肿瘤的生长、转移和血管生成,基于HA家族成员的抗肿瘤治疗已引起广泛关注。目前,针对HA家族成员的肿瘤治疗方法主要包括小分子抑制剂、抗体、靶向递送抗肿瘤药物等。     

Controlled release of chlorhexidine diacetate from a porous methacrylate system: supercritical fluid assisted foaming and impregnation

The release of chlorhexidine diacetate (CX) from a self-curing polymeric system based on poly(ethylmethacrylate) and tetrahydrofurfurylmethacrylate (PEM/THFM) was developed in this study. Supercritical fluid assisted impregnation and foaming was employed for preparing porous CX-PEM/THFM drug release system. X-ray diffraction (XRD) and differential scanning calorimetry (DSC) show that the crystallinity of CX significantly decreased after supercritical processing, whilst Raman spectroscopy suggested a hydrogen bonding interaction between the CX and PEM in the product. A UV-Vis dissolution study revealed that the drug release rate is almost as seven times faster in the SCF processed drug delivery system than conventional cured samples.     

Mechanism of adrenomedullin-stimulated hyaluronic acid release in rat mesangial cells

Adrenomedullin is a potent vasodilatory peptide that increases cAMP in a number of different systems including rat mesangial cells. Since mesangial cells play a significant role in glomerular matrix production, we evaluated the effects and molecular mechanisms of adrenomedullin action on hyaluronic acid release, an important extracellular matrix component. Adrenomedullin increased hyaluronic acid release in mesangial cells in a concentration-dependent manner. Forskolin, an adenylate cyclase activator, and dibutyryl-cAMP, a cell permeable cAMP analog, also increased hyaluronic acid release significantly. Adrenomedullin-stimulated hyaluronic acid release was inhibited by the adrenomedullin receptor antagonist, adrenomedullin-(22-52). Inhibition of protein kinase A with H89 [{N-[2-((p-Bromocinnamyl)amino)ethyl]-5-isoquinolinesulfonamide, hydrochloride}], a potent protein kinase A inhibitor did not affect adrenomedullin-stimulated hyaluronic acid release; however, H89 [{N-[2-((p-Bromocinnamyl)amino)ethyl]-5-isoquinolinesulfonamide, hydrochloride}] inhibited forskolin- and dibutyryl-cAMP-induced hyaluronic acid production. In addition, SB203580 {[4-(4-fluorophenyl)-2-(4-methylsulfinylphenyl)-5-(4-pyridyl)1H-imidazole}, a P38 mitogen-activated protein kinase (P38 MAPK) inhibitor attenuated adrenomedullin-, forskolin-, and dibutyryl-cAMP-stimulated hyaluronic acid release. Hyaluronic acid release induced by adrenomedullin, forskolin and dbcAMP was also inhibited by wortmannin {[1S-(1, 6b, 9aβ, 11, 11bβ)]-11-(Acetyloxy)-1, 6b, 7, 8, 9a, 10, 11, 11b-octahydro-1-(methoxymethyl)-9a, 11b-dimethyl-3H-furo[4, 3, 2-de]indeno[4, 5-h]-2-benzopyran-3, 6, 9-trione}. We conclude that adrenomedullin, forskolin and dbcAMP cause an increase in hyaluronic acid release in rat mesangial cells through a pathway that involves activation of wortmannin-sensitive kinase and P38 MAPK. Although cAMP stimulation and protein kinase A activation can induce hyaluronic acid release, adrenomedullin-stimulated hyaluronic acid release appears to be independent of protein kinase A activation. These data provide the first demonstration of the involvement of P38 MAPK- and wortmannin-sensitive kinase pathways in the stimulation of hyaluronic acid production by rat mesangial cells.     

透明质酸在肿瘤治疗药物新型给药系统中的应用

透明质酸（hyaluronic acid, HA）因其良好的理化性质和肿瘤靶向性,已作为药物载体或者靶向因子应用于肿瘤治疗的新型给药系统中,并成为肿瘤治疗研究的热点。本文主要对HA在新型给药系统的应用进行介绍。     

Self-assembled amphiphilic hyaluronic acid graft copolymers for targeted release of antitumoral drug

Polymeric micelles obtained by self-assembling of amphiphilic hyaluronic acid (HA) graft copolymers have been prepared and characterized. In particular, hyaluronic acid (HA) has been grafted to polylactic acid (PLA) and polyethylenglycol chains (PEG), then the copolymers able to form micelles in aqueous medium have been chosen to entrap the antitumoral drug Doxorubicin. The critical aggregation concentration of HA-g-PLA or HA-g-PLA-g-PEG micelles has been determined by using pyrene as a fluorescent probe, whereas their shape and size have been evaluated by light scattering measurements, scanning and transmission electron microscopies. The selective cytotoxicity of drug loaded micelles toward the CD-44 over-expressing HCT-116 cells compared to receptor deficient human derm fibroblasts has been demonstrated. Pegylated micelles showed better stability and drug loading capacity and they were able to escape from macrophage phagocytosis.     

巯基化透明质酸对牛血清白蛋白体外释药机制的研究

目的 研究基于巯基化透明质酸骨架片的牛血清白蛋白的体外释放特性.方法 以牛血清白蛋白(BSA)为模型药物,通过测定不同巯基取代度、不同pH下骨架片体外释放度,并采用零级动力学方程、一级动力学方程、Higuchi方程、Ritger-Peppas方程、威布尔方程拟合,阐明BSA体外释放的机理.结果 巯基化透明质酸能延缓BSA的释放,并随着结合物巯基含量的增加,释放速率减慢;巯基化透明质酸骨架片在pH6.8磷酸盐缓冲液中的释放速率大于在pH1.7氯化钾-盐酸缓冲液中的释放速率.结论 基于巯基化透明质酸骨架片的BSA的体外释放机制为骨架溶蚀.     

“Sponge-like” dressings based on biopolymers for the delivery of platelet lysate to skin chronic wounds

The aim of the present work was the development of sponge-like dressings, obtained by freeze-drying, based on chitosan glutamate and sodium hyaluronate for platelet lysate (PL) delivery to chronic skin wounds.     

Microneedles containing cross-linked hyaluronic acid particulates for control of degradation and swelling behaviour after administration into skin

Microneedles (MN) containing cross-linked hyaluronic acid (X-linked HA) particulates were prepared to control the degradation and swelling behaviour after transdermal drug delivery. The X-linked HA particulates were prepared by cross-linking HA chains and then passing the particulates through a sieve. Then, microneedles were prepared by micromolding method. The rheological properties of X-linked HA were studied. The penetration success rate, mechanical failure and dissolution rate of microneedles containing only hyaluronic acid (HA MN) and microneedles containing X-linked HA were compared. The delivery of fluorescein into the skin with X-linked HA MN was also observed using a confocal microscope. The size of the pulverised particulates in water ranged between 29 and 82?μm in diameter. The HA MN and X-linked HA MN were 270?μm in length. X-linked HA MN with fluorescein was inserted to a depth of 90% of the microneedle length successfully. There was no decrease in the penetration success rate for MN with up to 20% content of X-linked HA particulates. X-linked HA MN with up to 20% of particulate content did not change the dissolution time. Delay in degradation of HA, sustained drug release, and swelling behaviour of the skin layer can be obtained by X-linked HA MN.     

Methylprednisolone esters of hyaluronic acid in ophthalmic drug delivery: in vitro and in vivo release studies

Films and microspheres were prepared from various esters of hyaluronic acid. A model drug, methylprednisolone, was either physically incorporated into the polymer matrix or chemically bound to the polymer backbone through an ester linkage. In vitro release from films with covalently bound drug was much slower (t_50% = 71 h) than that for physically dispersed drug (t_50% = 2.5−17 h). Methylprednisolone concentrations in the tear fluid of New Zealand rabbits were measured after ocular application of drug (approx. 420 μg) in different dosage forms. When methylprenisolone was physically dispersed in the polymer matrix, in vivo drug release from matrices was slower than that observed in vitro. Compared with a suspension control, peak methylprednisolone concentrations in tear fluid were 9–14 times lower after administration of drug in polymer films and AUC_{0–8 h} values were 4–7 times higher. These results imply that hyaluronic acid ester preparations can increase the residence time of methylprednisolone in the tear fluid of rabbits.     

Effect of ionic crosslinking on the drug release properties of chitosan diacetate matrices

Chitosan diacetate (CDA) was prepared by alkylating the amino moieties of chitosan with mono-iodoacetic acid. Subsequently, CDA was cross-linked with Al3+, Zn2+, and Ca2+ ions to yield three ionotropically crosslinked polymeric matrices. These composite matrices were characterized employing infrared spectroscopy (IR) and differential scanning calorimetry (DSC). Subsequently, they were loaded with caffeine, as a model drug, and were assessed as sustained release carriers by evaluating their caffeine release profiles. Interestingly, only CDA-Zn2+ complex sustained the release of caffeine effectively in a zero-order manner. The drug release and thermal behavior of the tested matrices agree with the relative strength of the ionic or coordination character of the bonds. This, in turn, depends on the position of the complexing ions on the electrophilic softness/hardness scale.     

玻璃酸治疗骨关节炎的研究进展

骨关节炎(OA)是中老年人常见的慢性病,其发病率逐年增加。临床采用补充外源性玻璃酸(HA)的方法治疗OA已取得显著疗效。此文对近年来HA治疗OA的作用机制、HA相关制剂产品及其临床应用的最新研究进展进行综述。     

Economic evaluation of the treatment of chronic wounds: hydroactive wound dressings in combination with enzymatic ointment versus gauze dressings in patients with pressure ulcer and venous leg ulcer in Germany

OBJECTIVE: The treatment costs for pressure ulcers and venous leg ulcers were estimated based on the hospital administrator's perspective in Germany. DESIGN: A spreadsheet model using input data from various hospitals in Germany was developed. INTERVENTIONS: Five currently used treatment strategies were analysed: gauze, impregnated gauze, calcium alginate and hydroactive wound dressing with enzymatic ointment. PARTICIPANTS: All cases used for and in the analysis were treated in the inpatient setting (4 hospitals and 120 patients were included). MAIN OUTCOME MEASURES AND RESULTS: The outcome distributions were calculated using the Monte Carlo method. For the whole treatment process, the attributable costs for the hospital were calculated for different cases (severity) and all treatment strategies (1997 values). The costs for treatment with gauze were the highest, whereas the costs for treatment with hydroactive wound dressings and enzymatic ointment were the lowest. The relation between personnel and material costs for gauze is approximately 95 to 5% and for hydroactive wound dressings 67 to 33%, respectively. The cost savings per case were between 1196 deutschmark (DM) and DM9826 using hydroactive wound dressings instead of gauze dressings (depending on the severity of the pressure ulcer), and between DM135 and DM677 for venous leg ulcers. The results were robust and did not change in any performed sensitivity analysis (parameter: 'personnel costs per minute', 'time required for changing a wound dressing', 'total number of wound dressing changes'). CONCLUSIONS: Despite the higher material costs of the hydroactive wound dressings in combination with enzymatic wound cleaning compared with other wound dressings, they should be recommended for the treatment of pressure ulcers and venous leg ulcers. This therapy alternative brings about significant reductions in total costs for hospitals because of significant reductions in personnel costs and the duration of treatment.     

肉毒素联合透明质酸治疗颈纹的面部年轻化方案分析

目的研究肉毒素联合透明质酸治疗颈纹的面部年轻化方案。方法选取我院于2017年10月～2018年10月进行治疗的40例颈纹且面部年轻化需求患者,均进行肉毒素联合透明质酸治疗,观察所有患者治疗后效果与满意度情况。结果 40例患者中均存在不同颈纹明显,且皮下组织减少,皮肤松弛与肤色暗沉的情况,经过治疗后,显效30例,有效10例,无效0例,有效率为100.00%。术后随访半年,总有效率为34例(85.00%)。平均康复时间为(12.05±3.21)d。术后调查满意度,其中满意37例,一般2例,不满意1例,总满意度为39例(97.50%)。结论对于颈纹的面部年轻化方案可采取肉毒素联合透明质酸治疗,临床疗效显著,且患者康复时间较短,手术微创且安全,值得应用。     

体表慢性溃疡治疗方法的研究

目的 比较4种方法对体表慢性溃疡的疗效,研究治疗慢性溃疡的最好方法。方法将同期收治的患者120例随机分为4组,每组30例,应用不同的治疗方法,即A组湿润暴露疗法（MEBT／MEBO）＋高压氧（hyperbaric oxygen,HBO）,B组湿润暴露疗法（MEBT／MEBO）,C组重组牛碱性成纤维细胞生长因子（贝复济,bFGF）治疗,D组传统方法。观察创面用药后的症状改善情况,统计平均愈合时间及创面愈合的皮肤质量,并进行对比、总结。结果A组在减轻创面疼痛,预防创面瘢痕形成方面优于C、D组（P〈0．05）,在平均愈合时间方面优于B、C、D组（P〈0．05）。结论湿润暴露疗法＋高压氧是治疗体表慢性溃疡的最好方法。     

Study on the release of chlorhexidine base and salts from different liquid crystalline structures

The aim of this study was to investigate the influence of two types of chlorhexidine species, chlorhexidine base and its salts, on the physico-chemical features of liquid crystalline systems and on drug transport through lipophilic membranes.

A non-ionic surfactant, Synperonic A7 (PEG7-C13-15) was selected for the preparation of the liquid crystalline systems. Mixtures of different ratios of Synperonic A7 and water were prepared. The liquid crystalline systems were characterized using polarizing microscopy and dynamic oscillatory test. Membrane transport was also examined. The addition of chlorhexidine species to the liquid crystalline system modified the structure of the liquid crystalline system. As a result of the changes of liquid crystalline structures, the drug release of various types of chlorhexidine could be also modified. The combination of the base and salt forms of the drug in one dosage form could eliminate the drug release changes from liquid crystalline systems of dynamically changeable structures.     

New cytokine dressings. I. Kinetics of the in vitro rhG-CSF, rhGM-CSF, and rhEGF release from the dressings.

Wound repair-stimulatory activities of various cytokines and growth factors depend on successful delivery of these factors to the injured sites. Here were present the design and preparation of the new collagen- and polyurethane-based dressings containing the recombinant human cytokines-rhG-CSF, rhGM-CSF or rhEGF. To test the efficacy of the retrieval of the incorporated cytokines, their controlled release from the dressings was carried out over three consecutive days using polyurethane sponge as a collector of the extracts. The maximum quantities of the released rhG-CSF, rhGM-CSF and rhEGF reached approximately 25, 50, and 10%, respectively, of the total cytokine contents of the dressings, as assessed by the specific ELISA tests. These data indicate that collagen- and polyurethane dressings containing rhGM-CSF and rhG/CSF may serve as effective tools for the topical delivery of cytokines to wounded tissues. Copyright